CELLULAR MECHANISMS OF ANDROGEN ACTION IN BRAIN

Description

The hypothalamus and limbic brain play an important role in theregulation of gonadotropin secretion and reproductive behavior inthe male. Numerous pharmacological studies have suggested amajor role for monoaminergic neurons in mediating aspects ofboth of these processes. There is, however, a complex interactionbetween androgens and neurotransmitters within the brain. Notonly do changes in neurotransmission affect androgen-dependentprocesses, but changes in the levels of circulating testosteronecan affect some processes relating to catecholamine transmission.This grant proposes to study these aspects of the cellularmechanism of androgen action by determining (1) whethermonoamines affect the metabolism of androgens to activeestrogenic metabolites (aromatization) in the brain; and (2)whether testosterone (T) or its active metabolites, in turn,regulate the number and/or affinity of dopamine (D2) receptors inregions of the brain relevant to behavioral and neuroendocrinefunctions. To accomplish the first objective, experiments areoutlined that will measure aromatase activity and nuclearandrogen receptor concentrations under conditions wheremonoamine dynamics have ben altered by agonists, antagonists,and synthesis blockers. The second goal will be approached withstudies that will measure the binding parameters of dopamine (D2)receptors in male rats after various endocrine manipulations thatwill vary the androgen status on the animals. Pharmacologicintervention will be used to dissect out the contribution made byactive T metabolites. Finally, studies are proposed which willbegin to localize androgen modulated catecholamine bindingwithin specific hypothalamic nuclei. This studies proposed hereinwill lead to a better understanding of how androgens interact withneurotransmitters to regulate neuronal functions. Moreover theinformation gained should add to our knowledge to the centralcomponents in the physiology and pathophysiology of malereproduction and sexual development. In a larger sense, thisresearch has implications for our understanding of the cellularevents underlying the action of all gonadal steroids